DIP Database of Interacting Proteins 611 Young Drive East; Los Angeles CA 90095; USA http://dip.doe-mbi.ucla.edu/ dip@mbi.ucla.edu 611 Young Drive East; Los Angeles CA 90095; USA http://dip.doe-mbi.ucla.edu/ preusser-2001-1 in vitro In vitro fluorescence spectr classical fluorescence spectroscopy fluorescence spectr predetermined predetermined participant predetermined Preusser A., Briese L., Baur AS., Willbold D. DIP original experiment: DIP-266690X Journal of virology 2001 IMEx Direct in vitro binding of full-length human immunodeficiency virus type 1 Nef protein to CD4 cytoplasmic domain. Preusser A., Briese L., Baur AS., Willbold D. Only protein-protein interactions imex curation preusser-2001-2 in vitro In vitro nmr nuclear magnetic resonance NMR NMR nmr predetermined predetermined participant predetermined Preusser A., Briese L., Baur AS., Willbold D. DIP original experiment: DIP-266691X Journal of virology 2001 IMEx Direct in vitro binding of full-length human immunodeficiency virus type 1 Nef protein to CD4 cytoplasmic domain. Preusser A., Briese L., Baur AS., Willbold D. Only protein-protein interactions imex curation nef_hv1a2 Protein Nef nef Negative factor 3'ORF protein protein hv1a2 Human immunodeficiency virus type 1 group M subtype B (isolate ARV2/SF2) MGGKWSKRSMGGWSAIRERMRRAEPRAEPAADGVGAVSRDLEKHGAITSSNTAATNADCAWLEAQEEEEVGFPVRPQVPLRPMTYKAALDISHFLKEKGGLEGLIWSQRRQEILDLWIYHTQGYFPDWQNYTPGPGIRYPLTFGWCFKLVPVEPEKVEEANEGENNSLLHPMSLHGMEDAEKEVLVWRFDSKLAFHHMARELHPEYYKDC Down-modulates surface MHC-I molecules. Internalized molecules are sequestred to the trans-Golgi network (TGN). Also decreases cell surface CD4 antigen by interacting with the Src family kinase LCK thereby inducing LCK-CD4 dissociation and by increasing clathrin-dependent endocytosis of this antigen to target it to lysosomal degradation. Peroxisomal acyl-coenzyme A thioester hydrolase 1 (PTE1) seems to be involved in this process. May serve as a direct bridge between CD4 and the cellular endocytic machinery by interacting with beta-COP and adaptins. In consequence, surface MHC-I and CD4 are decreased and infected cells are masked for immune recognition by cytotoxic T lymphocytes. Decreasing the number of viral receptors prevents reinfection by more HIV particles Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interacts with the TCR-zeta chain to up-regulate the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules send attacking cytotoxic T-cell into apoptosis Protects the infected cell from apoptosis in order to keep it alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5. Interacts with p53 and decreases the half-life of the latter, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that induces phosphorylation of Bad mint homomint Early protein that seems to play a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Enhances virus infectivity and pathogenicity cd4_human T-cell surface glycoprotein CD4 CD4 T-cell surface antigen T4/Leu-3 protein protein human Homo sapiens Human MNRGVPFRHLLLVLQLALLPAATQGKKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQLLVFGLTANSDTHLLQGQSLTLTLESPPGSSPSVQCRSPRGKNIQGGKTLSVSQLELQDSGTWTCTVLQNQKKVEFKIDIVVLAFQKASSIVYKKEGEQVEFSFPLAFTVEKLTGSGELWWQAERASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLPQALPQYAGSGNLTLALEAKTGKLHQEVNLVVMRATQLQKNLTCEVWGPTSPKLMLSLKLENKEAKVSKREKAVWVLNPEAGMWQCLLSDSGQVLLESNIKVLPTWSTPVQPMALIVLGGVAGLLLFIGLGIFFCVRCRHRRRQAERMSQIKRLLSEKKTCQCPHRFQKTCSPI cd4-nef-1 3135455 N/A 3135457 unspecified role unspecified role unspecified role unspecified role ecolx Escherichia coli N/A 3135458 unspecified role unspecified role unspecified role unspecified role region Region 407-419 sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false P01730:p.Leu438_Leu439delinsAlaAla L413A/L414A mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength alanine scanning alanine scanning certain certain sequence position certain certain certain sequence position certain false Fluorescein-label Fluorescein-label fluorescein fluorescein label fluorescein n-term range n-terminal range n-term range n-term range n-terminal range n-term range false in vitro In vitro direct interaction direct interaction false false false cd4-nef-2 3135456 N/A 3135457 unspecified role unspecified role unspecified role unspecified role ecolx Escherichia coli N/A 3135458 unspecified role unspecified role unspecified role unspecified role Region 403-433 Region 403-433 sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false in vitro In vitro direct interaction direct interaction false false false